Data were collected on all treatment-naïve women referred to the clinic who were subsequently initiated on HAART during pregnancy (N=689). The mean age of the cohort was 29.2 years (standard deviation 5.0, range 18-48 years). The timing of HIV diagnosis was obtained in 388 women of whom 77.3% were diagnosed during the current pregnancy. Of 410 women with prior pregnancy data available, 11.5% (N=47) were primaparous. The mean number of pregnancies per woman was 2.7 (standard deviaton 1.1 and range 1-8). Only 1.6% (N=11) of multiparous women reported taking single dose nevirapine for PMCTC during a prior pregnancy. The mean baseline CD4+ cell count performed at first clinic visit for the majority of women was 154 cells/uL (n=639, SD 92, range 6 to 784 cells/uL), with 81.3% of women having CD4 counts below 200 cells/uL. The mean baseline HIV-1 viral load was 101,561 copies/ml and standard deviation 177,585 copies/ml. The distribution of viral loads was asymmetric, with a skew towards lower ranges, as demonstrated by the median baseline HIV-1 viral load (n=452) of 29,000 copies/ml.
The most common opportunistic infection (OI) at presentation was tuberculosis (7.7%). Serious OIs identified at baseline included cryptococcal meningitis (0.4%) and Kaposi's sarcoma (0.3%). Syphilis was the only sexually transmitted infection routinely screened in this cohort. Among 457 women with rapid plasma reagin (RPR) test results, 4.8% (N= 22) were positive. The most common non-infectious medical co-morbidities were hypertension (pre-existing/non-gestational hypertension 1.0% (N=7) and gestational hypertension (hypertension developing after 20 weeks of gestation without proteinuria) 3.0% (N=21). There were also six cases of preeclampsia (0.9%) and 2 cases of eclampsia (0.3%), with no maternal deaths or adverse fetal outcomes. No cases of gestational diabetes were reported (monitoring performed with urine dipsticks); however, three (0.4%) women in the cohort had pre-existing diabetes and there were no adverse outcomes among this group.
The mean gestational age at HAART initiation was 27 weeks (data available on 437 women) and the mean number of weeks on HAART during pregnancy was 10.4 (data available on 250 women). The most commonly utilized HAART regimen in the cohort was stavudine, lamivudine, and nevirapine (82% of 620 women for whom data were available) (). Follow-up CD4+ cell counts were done in most women who remained in the program for at least 24 weeks (N=244). Of these women, 80% gained at least 50 or more cells/uL a mean of 24 weeks after baseline, and half of this group (41.4%) gained 100-250 cells/uL. Approximately 8.2% of women experienced a drop in CD4 count.
Antiretroviral Regimens Utilized in the Antenatal Clinic at Johannesburg General Hospital
Baseline and follow-up HIV-1 viral load data were available in a subset of 211 women. At baseline 44% of these women had viral loads greater than 50,000 copies/ml. A mean of 14.4 weeks later, 80.5% were suppressed to <1000 copies/ml and only six women continued to have viremia at a level of greater than 100,000 copies/ml (). The most common adverse reaction among women in the cohort was nevirapine associated skin rash (18 episodes, 3.5%) including 2 women with Stevens-Johnson syndrome. Clinically significant nevirapine-associated hepatitis occurred in 1% of the cohort, with no deaths. Mitochondrial toxicities were rare with neuropathy reported in two women (0.3%), although the mean duration of exposure in the cohort was brief (ten weeks). Only 35 women received protease inhibitors at any point during pregnancy and no adverse reactions were reported. Regimen changes during pregnancy were uncommon, with only 2.6% (N=16, data available on 620 women) switching to a different regimen for serious toxicity.
Comparison of Baseline and Follow-up HIV-1 Viral Load Measurements on a Subset of Pregnant Women Started on HAART during Pregnancy (N=211).
Among 455 women in whom delivery information was available 56.9% (N=259) had normal vaginal deliveries, 25.7% (N=117) had non-emergent Caesarean sections for reasons unrelated to HIV infection (fetal position, failure to progress, postdates, prior Caesarean section), and 17.4% (N=79) had emergent Caesarean sections for pre-eclampsia/eclampsia, fetal distress, and placental abruption or placenta previa. Among the women on whom postpartum data was available (N=355), complications included postpartum haemorrhage 2.0 % (N =7), retained products of conception 0.3 % (N=1), postpartum psychosis 0.3% (N=1), and prolapsed uterus 0.3% (N=1).
Gestational age at delivery was available for 266 infants in the cohort. Among this group, 19.5% (N=52) were premature (delivered prior to 37 weeks). Adjusted for gestational age, three premature infants were below the third percentile for weight. There were no neonatal deaths among this group. Excluding premature infants, the mean birth weight was 3023 grams (standard deviation 479 grams). Forty-eight infants (13.5%) were low birth weight (<2500 grams), and none met criteria for very low birth weight (<1500 grams). One each of the following congenital abnormalities was noted in the newborns: enlarged kidneys, bilateral clubbed feet, extra digit, and absent left hand (secondary to amniotic band).
For 302 mother/infant pairs who completed six weeks of postnatal follow-up, the HIV-1 transmission rate was 5% (N=15) as determined by HIV-1 DNA testing. Sixty-seven women (9.7%) delivered infants prior to inception of the PNC in October 2005, and 116 (16.8%) had not reached six weeks post-partum by the time the dataset was closed in February 2007, and therefore infant HIV status was unavailable. There were eleven women with fetal or infant loss, including three reports of intrauterine fetal demise, three stillbirths, and five neonatal deaths. One neonatal death was in an HIV negative infant (cause unknown), the remaining four infant deaths had unknown HIV status. Two deaths were from unknown causes and two were attributed to infection (gastroenteritis and pneumonia). The remainder of women did not return for infant HIV testing at six weeks postpartum (N=191, 27.7%), and therefore were classified as lost to follow-up. ANOVA did not reveal significant differences in the ages or baseline viral loads among women with HIV-infected versus uninfected versus status-unknown infants. For baseline CD4 cell counts, the two sample t-tests did not reach significance after Bonferroni correction, although the uncorrected p-value for the comparison of the three groups was 0.0243, with the mothers of HIV-infected infants showing lower baseline cell counts ().
ANOVA Comparison of Characteristics of Women in Antenatal Clinic for women with (1) HIV-uninfected babies at 6 weeks follow-up (2) HIV-infected babies at 6 weeks follow-up (3) HIV-status unknown at 6 weeks (lost to follow-up)
Among those who completed follow-up infant HIV testing, the transmission rate for women who received more than seven weeks of HAART during pregnancy was 0.3% (N=1). Due to national policies limiting viral loads to twice-yearly, the cohort lacks viral load data at the time of delivery. Therefore no statistical analysis could be performed evaluating the relationship between viral load at or near the time of delivery and risk of infant HIV infection. All but two neonates received single dose nevirapine. Both of these infants had follow-up HIV testing at six weeks, with one testing positive. The majority of women (99%) chose to formula feed.